The metabolic fate and effects of 2-Bromophenol in male Sprague–Dawley rats

Abstract

1. The metabolic fate and urinary excretion of 2-bromophenol, a phenolic metabolite of bromobenzene, was investigated in male Sprague–Dawley rats following single intraperitoneal doses at either 0, 100, or 200 mg/kg.

2. Urine was collected for seven days and samples analysed using ¹H NMR spectroscopy, inductively coupled plasma (ICP)MS, and UPLC-MS.

3. ¹H NMR spectroscopy of the urine samples showed that, at these doses, 2-bromophenol had little effect on endogenous metabolite profiles, supporting histopathology and clinical chemistry data, which showed no changes associated with the administration of 2-bromophenol in this study.

4. The use of ICP-MS provided a means for the selective detection and quantification of bromine-containing species and showed that between 15 and 30% of the dose was excreted via the urine over 7 days of the study for both the 100 and 200 mg doses, respectively.

5. The bulk of the excretion of Br-containing material had occurred by 8 h post administration. UPLC-MS of urine revealed a number of metabolites of 2-bromophenol, with 2-bromophenol glucuronide and 2-bromophenol sulphate identified as the major species. A number of minor hydroxylated metabolites were also detected as their glucuronide, sulphate, or O-methyl conjugates. There was no evidence for the production of reactive metabolites.

Keywords:

• 2-Bromobenzene
• metabolism
• nephrotoxicity
• metabonomics

Acknowledgements

The authors would like to thank the Consortium for Metabonomic Toxicology for the provision of samples and histopathology data and Peter Webborn for useful discussions.

Disclosure statement

The authors report no declaration of interest.

Additional information

Funding

This work was supported through a CASE studentship for K.N. Adesina-Georgiadis from the Biotechnology and Biological Sciences Research Council and AstraZeneca.